ABSTRACT More than 80% of children diagnosed with a malignancy now survive five years, with most living well into adulthood. This has resulted in a growing population of childhood cancer survivors, estimated to approach half a million by 2020. Unfortunately, curative treatments result in toxicities that leave many survivors with a substantial burden of adverse physical and mental health outcomes. Morbidities commonly observed after childhood cancer treatment include neurocognitive impairment in 40-50% of survivors, emotional distress, and cardiovascular disease. These late effects are often comorbid and may interact to synergistically contribute to adverse health outcomes. Symptoms of insomnia, reported by approximately 30-45% of adult survivors of childhood cancer, are believed to be a key player in this dynamic. We have demonstrated that insomnia is associated with neurocognitive impairment in adult survivors of childhood cancer and that reduction in insomnia is associated with improved cognitive performance. In the general population, insomnia is also associated with increased cardiovascular symptoms, including a 45% increased risk of developing or dying from cardiovascular disease. We hypothesize that by treating insomnia, improvements will be observed in neurocognitive function, emotional distress, and biomarkers of cardiovascular risk. Cognitive Behavioral Therapy for Insomnia (CBTi) is an established non-pharmacologic treatment that focuses on addressing problematic thoughts and behaviors related to insomnia. However, limited access to and availability of health care professionals trained to deliver CBTi has led to development of internet-based CBTi, which has been found effective in treating insomnia and comorbid psychological and fatigue symptoms in the general population and in survivors of adult onset cancers. We are proposing to conduct a randomized clinical trial to evaluate the efficacy of an internet-based CBTi intervention (SHUTi) on insomnia in adult survivors of childhood cancer. Importantly, while SHUTi has been shown to be efficacious in other populations, symptoms of insomnia in adult survivors of childhood cancer may have persisted for several decades and often co-occur with other treatment-related late effects. Therefore, we propose to examine the direct impact of SHUTi on improving insomnia, and the mediating effect of improved insomnia on neurocognitive functioning. We also will examine the contribution of changes in emotional distress and biomarkers of cardiovascular health following treatment for insomnia to survivor quality of life. We will recruit 352 survivors with comorbid insomnia and neurocognitive problems from the Childhood Cancer Survivor Study (CCSS). Positive results from this study cohort and our use of an internet-based intervention are likely to generalize and be scalable to the large and geographically diverse population of childhood cancer survivors with chronic health conditions.